One of the most compelling problems in immunology is an understanding of the pathogenesis resulting from lymphocyte recognition of altered-self determinants. Immunologic mechanisms underlie many autoimmune diseases and have also been implicated as promotors of lymphoid-cell neoplasia. SJL/J mice offer a unique opportunity to dissect the cellular requirements and sequelae associated with T cell recognition of syngeneic B cell surface antigens. SJL T lymphocytes proliferate in vitro when they are co-cultured with autologous B cells. In addition, the B lymphocyte-derived reticulum cell sarcomas (RCS), which occur in high incidence in this strain, express Ia antigens that appear to elicit a vigorous proliferative response in syngeneic T cells. This T cell response occurs upon in vitro co-culture of RCS cells and syngeneic thymus, lymph node or spleen cells. T cell proliferation can also be observed in vivo following injection of irradiated RCS cells into syngeneic recipients. Experiments will be undertaken to determine whether the T cell response to syngeneic B cells or to B cell-derived RCS tumors initiates cellular interactions which promote autoimmune disease and trigger the appearane of neoplastic lesions in syngeneic hosts. This hypothesis will depend on demonstrating: (1) that responding T cells produce soluble mediators (lymphokines) which affect host bystander cells, (2) that under the influence of responding T cells, host B lymphocytes are recruited for the production of autoreactive antibodies and (3) that the T cell responses to syngeneic determinants precipitate the appearance of B cell lymphomas of host origin. Detailed analysis of T cell reactivity to syngeneic antigens will provide an appropriate foundation for future investigations to elucidate agents that may cause subtle self-alterations which induce autoresponsiveness and how the recruitment of bystander cells promotes oncogenesis.